CLINICAL NEWS
HCT Outcomes in Patients With Autoimmune Diseases Vary With Location , Treatment Center Volume
Hematopoietic cell transplantation ( HCT ) has been evaluated as a treatment option for patients with autoimmune diseases ( ADs ) that respond poorly to conventional immunosuppressive treatments and supportive care . However , HCT use varies widely based on geography and disease type .
In an analysis of data from the European Society for Blood and Marrow Transplantation ( EBMT ) registry , John A . Snowden , MBChB , MD , from the Department of Hematology at the Sheffield Teaching Hospitals National Health Service Foundation Trust in the United Kingdom , and co-authors assessed trends and outcomes associated with HCT for a variety of ADs . They found that center experience , accreditation , and a country ’ s socioeconomic status are related to HCT outcomes .
The findings “ confirm that [ use of ] HCT for severe ADs is sustained and increasing , despite the introduction and widespread adoption of biologic and other modern therapies ,” wrote Dr . Snowden about the study published in Blood Advances .
EBMT is a not-for-profit society representing more than 600 HCT centers in Europe and other areas , and the registry includes data on more than 2,000 patients over the course of more than 20 years . Since 1994 , 247 centers in 40 countries have reported data on HCT in this setting .
The researchers analyzed data from 1,951 patients with ADs undergoing their first autologous HCT ( AHCT ; median age = 37 years ; range = 3-76 years ) or allogeneic HCT ( alloHCT ; median age = 12 years ; range = < 1-62 years ) between January 1994 and December 2015 . Most HCT activity ( 74 %) took place in Italy , Germany , Sweden , the United Kingdom , the Netherlands , Spain , France , and Australia .
Reasons for undergoing HCT included multiple sclerosis ( MS ; n = 839 ), connective tissue disorders ( n = 596 ), inflammatory arthritis ( IA ; n = 178 ), vasculitis ( n = 46 ), inflammatory bowel disease ( n = 191 ), hematologic immune cytopenia ( n = 97 ), and type 1 diabetes ( n = 20 ).
There were two peaks of activity , the authors reported : one in 1999 when IA was the most common indication and then a “ gradual upward trend ” from 2006 to 2015 as MS , systemic sclerosis , and Crohn ’ s disease became the most common indications .
The national transplant rates between 2010 and 2015 varied substantially among participating countries , and they correlated with countries ’ socioeconomic status , per the Human Development Index ( a measurement evaluating a country ’ s achievements in longevity , knowledge , and standard of living ; p = 0.006 ). However , there was no significant association between transplant rates and the Health Care Expenditure ( HCE ; the total annual consumption of health goods and services plus capital investment in health-care infrastructure ; p = 0.2 ) or team density ( the number of transplant teams divided by the population ; p = 0.2 ).
After a median follow-up of 34 months ( range = 1-234 months ), the global three- and five-year overall survival ( OS ) rates for the 1,839 patients undergoing AHCT were 89 percent and 86 percent , respectively , and three- and fiveyear progression-free survival ( PFS ) rates were 57 percent and 49 percent .
Relapse incidence ( RI ) rates at three and five years were 38 percent and 46 percent , and nonrelapse mortality ( NRM ) rates were 4.6 percent and 5.3 percent .
“ In support of a learning and experiential curve , there was
TABLE . AHCT Outcomes in Different Time Periods significant improvement in NRM along with PFS and relapse rate [ across time periods ],” the authors reported ( see TABLE ). Several other factors were associated with better PFS outcomes , including AHCT performed for the most common indications ( MS , systemic sclerosis , and Crohn ’ s disease ; p = 0.001 ), younger patient age ( p = 0.001 ), greater center experience ( defined as ≥23 transplants conducted for specific AD ; p = 0.001 ), longer center learning ( defined as time from first HCT for AD ≥6 years ; p = 0.01 ), and JACIE ( the Joint Accreditation Committee of the International Society for Cellular Therapy and EBMT ) accreditation status ( p = 0.02 ).
“ Economic factors may influence outcome ,” the researchers added : In a univariate analysis of patients with MS and systemic sclerosis , AHCT performed in countries with lower HCE was associated with increased risk of NRM and inferior PFS rates . “ Such association of economic factors with outcome in the field of ADs requires further investigation .”
Though there were limited data on patients undergoing alloHCT , long-term outcomes showed global three- and five-year OS rates of 67 percent and 64 percent , respectively , PFS rates of 59 percent and 56
|
1994-1999 |
2000-2004 |
2005-2010 |
2011-2015 |
100-day non-relapse mortality ( NRM ) |
6.4 % |
3.7 % |
3.2 % |
1.3 % |
3-year NRM |
7.1 % |
5.6 % |
4.9 % |
3 % |
Relapse incidence |
52.2 % |
39.3 % |
32.2 % |
34.2 % |
Progression-free survival |
40.6 % |
55.1 % |
62.9 % |
62.8 % |
Overall survival |
87 % |
88.4 % |
89.6 % |
90.3 % |
AHCT = autologous hematopoietic cell transplantation percent , and RI rates of 21 percent and 24 percent . NRM rates rose from 13 percent at 100 days , then plateaued at 20 percent at three and five years . As with AHCT , outcomes appeared to improve over subsequent time periods . Better relapse outcomes were observed in patients younger than 18 years ( p = 0.002 ), but no effect was observed with regard to center experience ( defined as ≥2 patients ).
“ The future of HCT in ADs very much depends on the ‘ dynamic ’ with alternative treatment options , including the new biologic agents ,” the researchers concluded . “ Moving forward , there is now a strong argument for a focus on ‘ implementation science ’ to methodically
“[ The use of ] HCT for severe autoimmune diseases is ... increasing , despite the introduction [ of ] modern therapies .”
— JOHN A . SNOWDEN , MBChB , MD
drive the field of HCT for AD into routine , fully funded , high-quality clinical practice , across [ specialties ].” They added , though , that HCT for ADs is likely to be more resourceintensive than standard HCT , which may slow its uptake .
The study is limited by its retrospective design and reliance on information from a registry database . ●
Dr . Snowden reports receiving funding from Sanofi and Jazz Pharmaceuticals .
REFERENCE
Snowden JA , Badoglio M , Labopin M , et al . Evolution , trends , outcomes and economics of haematopoietic stem cell transplantation in severe autoimmune diseases . Blood Advances . 2017 December 20 .
ASHClinicalNews . org ASH Clinical News
37